Abstract
A 4-fold symmetric arrangement of TVGYG polypeptides forms the selectivity filter of the K+ channel from Streptomyces lividans (KcsA). We report the synthesis and properties of synthetic models for the filter, p-tert-butyl-calix[4]arene-(OCH(2)CO-XOBz)(4) (X = V, VG, VGY), 1-3. The first cation (Na+, K+) binds to the four -[OCH(2)CO]- units, a region devised to mimic the metal-binding site formed by the four T residues in KcsA. NMR studies reveal that cations and valine amide protons compete for the carbonyl oxygen atoms, converting NH(Val)...O=C hydrogen bonds to M+ ...O=C bonds (M+ = Na+ or K+). The strength of these interchain NH(Val)...O=C hydrogen bonds varies in the order 3 > 2 > 1. We propose that such interchain H-bonding may destabilize metal binding in the selectivity filter and thus help create the low energy barrier needed for rapid cation translocation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Bacterial Proteins / chemistry
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Bacterial Proteins / metabolism*
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Binding Sites
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Bridged-Ring Compounds / chemical synthesis
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Bridged-Ring Compounds / chemistry
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Bridged-Ring Compounds / metabolism*
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Calixarenes*
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Cations / chemistry
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Dipeptides / chemical synthesis
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Dipeptides / chemistry
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Dipeptides / metabolism*
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Hydrogen Bonding*
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Ion Transport*
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Magnetic Resonance Spectroscopy
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Models, Chemical*
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Models, Molecular
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Oligopeptides / chemical synthesis
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Oligopeptides / chemistry
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Oligopeptides / metabolism*
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Peptide Fragments / chemistry
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Potassium / chemistry
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Potassium / metabolism*
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Potassium Channels / chemistry
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Potassium Channels / metabolism*
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Protein Binding
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Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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Streptomyces / chemistry
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Templates, Genetic
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Valine / analogs & derivatives
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Valine / chemical synthesis
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Valine / chemistry
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Valine / metabolism*
Substances
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4-tert-butylcalix(4)arene tetravaline benzyl ester
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4-tert-butylcalix(4)arene tetravaline-glycine benzyl ester
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4-tert-butylcalix(4)arene-tetravaline-glycine-tyrosine benzyl ester
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Bacterial Proteins
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Bridged-Ring Compounds
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Cations
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Dipeptides
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Oligopeptides
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Peptide Fragments
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Potassium Channels
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prokaryotic potassium channel
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Calixarenes
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Valine
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Potassium